DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/10/25 has been entered.
Election/Restrictions and Claim Status
Applicants’ amendments and arguments filed 10/7/25 are acknowledged. Any objection or rejection from the 7/2/25 office action that is not addressed below is withdrawn based on the amendments.
Previously, Group 1 and SEQ ID NO:64 were elected. A peptide consisting of SEQ ID NO:64 was found to be free of the prior art. Venema et al. (cite 8 of IDS 3/2/22; ‘Venema1996’) shows in Table 1 amino acids believed to be critical for binding activity. The region encompasses 14 amino acids so there is no adequate teaching, suggestion or motivation to make peptides comprising instant SEQ ID NO:1 that are less than 14 amino acids as claimed. In accord with MPEP 803.02, the search was extended to the extent necessary to determine patentability.
Claims 8-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 12/16/24.
Claim 2 has been canceled.
Claims 1, 3-7 and 13-15 are being examined.
Priority
The priority information is found in the filing receipt dated 5/10/22.
Claim Objections
Claims 14-15 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 5 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 5 appears to recite both broad and narrow limitations. Claim 5 uses the narrow recitation of ‘said construct is selected from’ 3 options (last 3 lines of the claim) thus suggesting that the construct is identical to one of the 3 constructs. However, the claim also broadly recites ‘cell penetrating peptide, a lipid, or a combination thereof’. None of the 3 recited constructs include a cell penetrating peptide or a combination of cell penetrating peptide and lipid. Further, the lipid as recited in the last 3 lines is limited to ‘myr’. In addition, claim 5 broadly refers to 7 to 19 amino acid peptide, but the recited constructs are 15, 12 and 7 amino acids in length. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. In the instant case, claim 5 has been interpreted as being limited to the 3 recited constructs.
Claim Rejections - 35 USC § 103
Claims were previously rejected under 35 USC 103. Since the claims have been amended the rejection is updated to correspond to the instant claims.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 3-7 and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Venema et al. (cite 8 of IDS 3/2/22; ‘Venema1996’) in view of Lowry et al. (‘Endothelial nitric-oxide synthase activation generates an inducible nitric-oxide synthase-like output of nitric oxide in inflamed endothelium’ JBC v288(6) February 8 2013, pages 4174-4193; ‘Lowry’) in view of Nelson et al. (cited with IDS 12/16/24; ‘Nelson’).
Venema1996 teach identification and characterization of calmodulin (CaM) binding domains of nitric oxide synthases (title and abstract). Venema1996 teach that to establish the location of CaM binding domains that peptides were prepared and tested for the ability to produce an electrophoretic mobility shift (last complete paragraph of page 6436 and figure 1). Venema1996 teach that a peptide corresponding to eNOS residues 493-512 was identified as the CaM binding region (abstract). Venema1996 teach that the peptide is a potent inhibitor of CaM mediated activation of nitric oxide synthase and has nM dissociation constants for CaM binding (abstract). Venema1996 teach the sequence of residues 493-512 as TRKKTFKEVANAVKISASLM (3rd complete paragraph of page 6436). Venema1996 teach that peptides were synthesized (pages 6435-6436 connecting paragraph) and teach that the peptide eNOS 493-512 was incubated with CaM (figure 1a). Venema1996 teach the identification of amino acids essential for CaM binding the eNOS CaM-binding domain (page 6439). In table I, Venema1996 shows amino acids believed to be critical for binding activity which includes residues at positions numbered 1, 8 and 13-14. For bov eNOS 493-512 the residues correspond to FKEVANAVKISASL (Table I).
Venema1996 does not teach a specific peptide as claimed with a cell penetrating peptide or lipid.
Lowry teach that eNOS activation generates on output of nitric oxide in inflamed endothelium (title and abstract). As shown in figure 13 and the caption (page 4189), Lowry teach that eNOS and CaM interact in cells (figure 1b) and show that high output of nitric oxide (NO) can impair cell migration and prevent proper angiogenesis and wound healing (figure 13 and last complete paragraph on page 4190). Lowry mentions blocking NO with an eNOS inhibitor (abstract). Lowry teach that the significance relates to eNOS derived NO impairing angiogenesis and wound healing (abstract).
Nelson teach that translocation of molecules to the interior of living cells is a necessity for many biochemical investigations (abstract). Nelson teach that cell penetrating peptides such as TAT are known to be conjugated to biomolecules for delivery into cells (first paragraph after abstract). Nelson teach that studies suggest that conjugated peptides insert into membranes by virtue of the myristoyl tag (first paragraph on page 14772). Nelson teach that a peptide with a terminal amino acid that was myristoylated was efficiently loaded into cells (first complete paragraph on page 14774 and figure 2). Nelson teach that the myristate group may provide advantages to CPPs including a more effective distribution within the cell (last complete paragraph on page 14779). Nelson teach methods of preparing the peptides (page 14772 2nd column 1st paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Venema1996 because Venema1996 teach that the peptide (eNOS residues 493-512) is a potent inhibitor of CaM mediated activation of nitric oxide synthase and has nM dissociation constants for CaM binding (abstract). With respect to the length of the peptide, Venema1996 teach the identification of amino acids essential for CaM binding the eNOS CaM-binding domain (page 6439). In table I, Venema1996 shows amino acids believed to be critical for binding activity which includes residues at positions numbered 1, 8 and 13-14. For bov eNOS 493-512 the residues correspond to FKEVANAVKISASL (Table I). Thus one would have been motivated to make peptides including the critical residues including FKEVANAVKISASL and FKEVANAVKISASLM. Based on the known functionality one would have been motivated to use such peptide for applications where such function is desired. Lowry teach that eNOS and CaM interact in cells (figure 1b) and show that high output of nitric oxide (NO) can impair cell migration and prevent proper angiogenesis and wound healing (figure 13 and last complete paragraph on page 4190). Lowry mentions blocking NO with an eNOS inhibitor (abstract). Lowry teach that the significance relates to eNOS derived NO impairing angiogenesis and wound healing (abstract). Thus one would have been motivated to make a peptide for such application. Since Lowry shows the eNOS CaM interaction inside cells (figure 13b) one would have been motivated to prepare the peptide for such purpose. Nelson teach that cell penetrating peptides such as TAT are known to be conjugated to biomolecules for delivery into cells (first paragraph after abstract). Nelson teach that studies suggest that conjugated peptides insert into membranes by virtue of the myristoyl tag (first paragraph on page 14772). Nelson teach that a peptide with a terminal amino acid that was myristoylated was efficiently loaded into cells (first complete paragraph on page 14774 and figure 2). Nelson teach that the myristate group may provide advantages to CPPs including a more effective distribution within the cell (last complete paragraph on page 14779). Thus one would have been motivated to add a myristoyl tag (or a TAT sequence) to either terminal end of the peptide of Venema1996 resulting in myr-FKEVANAVKISASL and myr-FKEVANAVKISASLM. One would have had a reasonable expectation of success since Nelson teach methods of preparing the peptides (page 14772 2nd column 1st paragraph).
In relation to claims 1, 4-5 and 13, as discussed above the prior art suggest myr-FKEVANAVKISASL and myr-FKEVANAVKISASLM which are 14 and 15 amino acids in length and comprise instant SEQ ID NO:1 and contain a lipid (myr) which is not naturally associated with the peptide. myr-FKEVANAVKISASLM is instant SEQ ID NO:62 recited in claim 5 and comprises SEQ ID NO:3 of claim 4.
In relation to claim 3, Nelson teach the TAT sequence which is arginine-rich (page 14771 first column) and this comprises charged amino acid residues.
In relation to claims 6-7, Nelson teach the preparation of the peptides in water (2nd column first paragraph on page 14772).
Response to Arguments - 103
Applicant's arguments filed 10/7/25 have been fully considered but they are not persuasive with respect to the rejection set forth above.
Although applicants argue that the claims have been amended specifically with respect to the length of the peptide needed for binding, the amended claims are addressed above. Venema et al. (cite 8 of IDS 3/2/22; ‘Venema1996’) shows in Table 1 amino acids believed to be critical for binding activity and the region encompasses 14 amino acids. Thus, one would not have been limited to making peptide of 20 amino acids in length.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RONALD T NIEBAUER whose telephone number is (571)270-3059. The examiner can normally be reached M - F 6:30 - 2:30 EST.
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RONALD T. NIEBAUER
Primary Examiner
Art Unit 1658
/RONALD T NIEBAUER/Examiner, Art Unit 1658